POS0869 GENETIC PREDICTED CAUSAL ASSOCIATION BETWEEN PSORIATIC ARTHRITIS AND CARDIOVASCULAR DISEASE
Authors: X. Y. Yin, Y. G. Feng, J. N. Liu, Q. Y. Su, Q. Yu, P. F. He, X. Li, S. X. Zhang
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Psoriatic arthritis (PsA) is an inflammatory musculoskeletal disease mediated by immune factors[1]. However, the results of previous studies of the associations of PsA and risk of cardiovascular Disease(CVD) have been conflicting[2]. The CVDs risk directly attributable to PsA remains to be determined, for the reason that observational epidemiological studies are prone to confusion and reverse causality[3]. In this study, we conducted a bi-directional Mendelian randomization (MR) analysis to explore causal inference between these two traits. <h3>Objectives</h3> This study aimed to estimate the bidirectional genetic association between PsA and CVD. <h3>Methods</h3> We selected independent single nucleotide polymorphisms(SNPs) related to the significance level of the PsA whole genome as the instrumental variables in the FinnGen project. Genetic association estimates for 12 CVD were obtained from a large consortium and the UK biobank. Analyses were conducted using the inverse variance-weighted(IVW), weighted median, and MR-Egger. Heterogeneity and pleiotropy between studies were assessed using Cochrane Q and MR Egger intercept. The leave-one-out analysis was performed to evaluate whether a single SNP interfered with the causal effect. MR-PRESSO was used to detect and eliminate SNPs that may bring significant pleiotropy. <h3>Results</h3> PsA increased the genetic susceptibility to myocardial infarction(MI), heart failure(HF), and atrial fibrillation(AF). The logarithmic odds ratios(OR) of PsA increased by one unit, and the risk of HF increased by 2.72% (OR=1.027, 95% CI=1.013-1.042, p&lt;0.001). The ORs per 1-SD increase of log-transformed PsA were 1.021 (OR=1.021, 95% CI=1.008-1.034, p=0.002) for AF and 1.001(OR=1.001,95% CI=1.000-1.001 p=0.016) for MI in the IVW analysis. In contrast, patients with PsA had a lower risk of pulmonary embolism (PE) (IVW: OR=0.948, 95% CI=0.910-0.988 p=0.011). There was no causal genetic relationship between PsA and other CVDs, such as stroke and its subtypes, coronary artery disease(CAD), coronary heart disease(CHD), and hypertension(all p&gt;0.05). After multiple tests and corrections, these associations persisted. In the reverse MR, we did not observe any significant causal relationship between CVD and PsA. <h3>Conclusion</h3> This study revealed suggestive evidence that PsA may increase the risk of MI, HF, and AF but reduce the risk of PE. Chronic inflammation caused by the continuous increase of proinflammatory cytokines and immune cells may be the primary way to connect this causal relationship. <h3>References</h3> [1]Ocampo, D. V. &amp; Gladman, D. Psoriatic arthritis. F1000Res 8, doi:10.12688/f1000research.19144.1 (2019). [2]Gladman, D. D. et al. Cardiovascular morbidity in psoriatic arthritis. Ann Rheum Dis 68, 1131-1135, doi:10.1136/ard.2008.094839 (2009). [3]Venkatesh, S. S. et al. Obesity and risk of female reproductive conditions: A Mendelian randomisation study. PLoS Med 19, e1003679, doi:10.1371/journal.pmed.1003679 (2022). <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.